The mechanism of viral DNA replication in Epstein-Barr virus (EBV) transformed lymphocytes will be investigated. Little is known about viral DNA replication within cells transformed by DNA tumor viruses. EBV, as an important human pathogen, has a number of characteristics that make it possible to study the intracellular behavior of its DNA; for example, many cell lines carry large numbers of copies of the viral genome, and probably many of these copies are carried in plasmid form. Methods for separation of viral from host DNA are being developed. Studies of viral DNA replication as related to that of the host, viral replicative intermediates, viral DNA membrane attachment, and expression of viral functions related to DNA synthesis within the transformed cell are proposed. The effects of various drugs such as phosphonoacetic acid and cyclophosphamide on viral and cellular DNA synthesis will be investigated. Information gained from such studies with drugs should be useful in testing for anti-herpes virus and anti-tumor agents.